The multiplicity of genetic, biochemical, metabolic, and morphological changes found in some 35 different lines of rat hepatoma have led to alterations in some of our previously held concepts of neoplastic transformation. Initial autoradiographic findings in this Division showed that in 8 tumors whose growth rates vary by a factor of 14, the thymidine labeling indices vary by a factor of only 4. The cell cycle times for the 2 most rapidly growing tumors (H-35 plus c2 and 3924A) have been found to be similar to that of normal rat liver; all have cell cycle times of 21-23 hours. The projected studies will also incude intermediate growth rate Hepatoma 9098, and slow growth rate Hepatoma 7787. Determinations of the changes in tumor volume with time will permit determination of the rate of cell loss in addition to the rate of cell proliferation, so that a more precise understanding of the kinetics of net tumor growth rates in these hepatomas can be obtained. Continuing efforts will be made to improve the accuracy and precision of analysis of the results in three areas: (1) more precise mathematical analysis of the per cent labeled mitotic curves in order to obtain cell cycle times, different phases of the cell cycle, growth fractions, and cell loss fractions; (2) greater correlation of tumor weight, size, and volume; and (3) further attempts to modify mathematical models for cell proliferation and tumor growth. The perturbations in cellular kinetics and tumor growth by radiation, 5-fluorouracil, and hydroxyurea will be determined in these three hepatomas (3924A, 9098, and 7787) which vary markedly with regard to growth rates, genetic characteristics, and thymidine labeling indices. These studies are designed to determine the changes in such factors as cell cycle time, different phases within the cell cycle, growth fraction, and cell loss fraction. It is possible that more effective clinical scheduling of radiation, alone or in combination with different chemotherapeutic agents, may eventually be derived from information which will be gained from these studies.